Vessel co-option negatively affects survival in patients with advanced hepatocellular carcinoma

Vessel co-option is a type of tumor vascularization that involves the incorporation of preexisting vessels from surrounding tissue rather than the induction of new vessel growth. This study aimed to identify the prevalence of vessel co-option patterns in patients with hepatocellular carcinoma and to evaluate the association of vessel co-option with resistance to systemic therapy and prognosis.

Tumor vascularization patterns at the time of initial hepatectomy were pathologically evaluated in patients who underwent systemic therapy for recurrence after liver resection, and their prognosis was examined. Gene expression profiles of tumor tissue were analyzed using RNA sequencing.

Among the 64 patients, 16 patients (25.0%) exhibited the vessel co-option pattern, and 48 patients (75.0%) had the angiogenesis pattern. No significant differences in patient background and tumor characteristics were observed between the groups. The disease control rate (53.3% vs. 56.5%, p = 1.00) and response rate (13.3% vs. 26.1%, p = 0.48) for systemic therapy were similar between the groups. While no significant difference in median PFS during systemic therapy was observed between the vessel co-option group and the angiogenesis group (4.7 vs. 4.1 months, p = 0.81), the median OS was significantly shorter in the vessel co-option group than in the angiogenesis group (12.8 months vs. 27.3 months, p = 0.018). In the vessel co-option group, RNA sequencing revealed enrichment of genes associated with cell surface interactions at the vascular wall, extracellular matrix, and neutrophil degranulation.

Compared with the angiogenesis pattern, the vessel co-option pattern was associated with worse OS in patients with advanced HCC, suggesting that vessel co-option reflects a biologically aggressive tumor phenotype.